Discovery of a Novel Mode of Fungal Cell Death Induced by Saturated Fatty Acids That Disrupt Cellular and Organ Function

June 4, 2025

Insights into Endoplasmic Reticulum Function and Potential for Drug Development

A collaborative research group from the University of Tokyo, Hiroshima University, and the RIKEN CSRS has discovered that pentadecanoic acid (C15:0) is toxic to fission yeast (Schizosaccharomyces pombe), a type of fungus. The researchers found that it generates an abnormal endoplasmic reticulum (ER) structure, which they named a 'giant ER sheet', and revealed that this structure physically blocks cell division, ultimately leading to cell death.

While fatty acids are essential for living organisms, excess amounts can cause illness through cell and tissue dysfunction, resulting in cell death — a phenomenon known as lipotoxicity. However, the molecular mechanisms underlying lipotoxicity remain largely unexplored, and there have been few reports of lipotoxicity in fungi. In this context, the present study demonstrates a novel mode of fungal cell death characterised by the formation of a 'giant ER sheet'. These findings contribute to a deeper understanding of cellular functions and hold promise for developing pharmaceuticals and agrochemicals that inhibit the growth of pathogenic fungi.

 

Original article

Proceedings of the National Academy of Sciences
DOI: 10.1073/pnas.2422126122

Y. Hoshikawa, N. Shirota, H. Tsugawa, S. Kimura, A. Matsuyama, Y. Yashiroda, H. Kakeya, M. Arita, R. Iizumi, M. Yoshida, S. Nishimura,

"Formation of giant ER sheets by pentadecanoic acid causes lipotoxicity in fission yeast".

Contact

Minoru Yoshida
Division Director
Drug Discovery Platforms Cooperation Division